PubMed Health⌕ Search

Biomedical subjects

F Bridey

Publications and source records attributed to F Bridey.

At least 19 recordsLinked to original sources
PubMed2005

Pharmacokinetic studies on Wilfactin, a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods.

OBJECTIVE: In order to correct the primary von Willebrand factor (VWF) defect and avoid supra-physiologic plasma levels of factor VIII, a pure VWF concentrate almost devoid of FVIII was developed and used in France since 1989. METHODS: The pharmacokinetic (PK) profile of the most recent version of this concentrate (Wilfactin; LFB, Les Ulis, France), treated with three virus-inactivation/removal methods (solvent/detergent, 35 nm filtration, dry heat treatment), was investigated in 25 patients. Seventeen patients with various types of clinically severe von Willebrand disease (VWD) were included in a crossover, randomized trial carried out in five European centers and comparing Wilfactin with concentrates containing both FVIII and VWF (FVIII/VWF). Eight type 3 VWD patients were included in another trial carried out in six French centers comparing Wilfactin with its previous version (Facteur Willebrand-LFB; LFB) that adopted one virus-inactivation method only. RESULTS: For both the measurements evaluated in this study (VWF antigen, VWF:Ag; and VWF ristocetin co-factor activity, VWF:RCo), Wilfactin had a PK profile similar to that of the FVIII/VWF concentrates and of Facteur Willebrand-LFB. VWF:RCo and VWF:Ag recoveries were 2.1 +/- 0.3 and 1.8 +/- 0.3 per IU kg(-1), respectively, and the half-lives were 12.4 +/- 1.8 and 15.9 +/- 1.5 h. The FVIII synthesis rate was 5.8 +/- 1.0 IU dL(-1) h(-1), with a half-life of 15.8 +/- 2.4 h. CONCLUSION: The PK of VWF and FVIII have not been altered by the three virus-inactivation/removal steps during the manufacturing of Wilfactin.

Adult↗
PubMed1998

Prevalence of antiphospholipid-related antibodies in unselected patients with history of venous thrombosis.

Antiphospholipid antibodies (aPL) are heterogeneous and are now accepted to be mainly phospholipid-protein-dependent antibodies. Although these antibodies are classically associated with thrombosis, their clinical relevance remains to be established. The subgroups of antibodies characterized by their proteic targets were reported to be more appropriate thrombotic markers. We analysed the prevalence of a large panel of antiphospholipid-related antibodies (aPLR), comprising antibodies directed to phospholipid-protein complexes and to different protein cofactors (beta2GPI, prothrombin, annexin V and protein S), in 122 consecutive unselected patients who had experienced at least one venous thrombotic event. The presence of lupus anticoagulants was assessed with an integrated assay using hexagonal phase phospholipids. Two types of aPL (APA and anti-beta2GPI-PL) were measured using a mixture of phospholipids containing cardiolipin and goat serum or human beta2GPI, respectively, as a source of protein cofactor. Our results show a similar prevalence, close to 15%, of lupus anticoagulants, APA and anti-beta2GPI-PL. In contrast, antibodies to beta2GPI were detected in only 8% of the patients, and very few patients had antibodies directed to other proteins. Of the 35 patients having at least one positive aPLR, 17 were classified as severe, because they had recurrent or early onset of thrombosis (< 35 years). The distribution of aPLR between severe and mild cases was not significantly different except for lupus anticoagulants. Our results clearly indicate that lupus anticoagulant is the only aPLR test to be strongly associated with the severity of thrombosis.

Annexin A5↗
PubMed1998

Development of a method to separate lipoprotein-bound and lipoprotein-depleted tissue factor pathway inhibitor. Measurement of free tissue factor pathway inhibitor activity.

The aim of this study was to develop a method to separate lipoprotein-bound from lipoprotein-free tissue factor pathway inhibitor (TFPI) and to measure the TFPI chromogenic activity and antigen in both fractions. This was performed by ultracentrifugation of plasma, after increasing its density to 1.21 g/ml with potassium bromide. Blood was taken from nine volunteers before and after an injection of low-molecular-weight heparin. The ultracentrifugation procedure was adequate, since the mean cholesterol recovery was 91% and only 2% of the cholesterol remained in the lipoprotein-depleted fraction. No free TFPI protein was found in the lipoprotein-rich fraction. Moreover, the amount of free TFPI in the lipoprotein-depleted fraction was close to that found in plasma. Using this method, we confirmed that heparin does not induce an increase in bound TFPI and that the moderate increase in total TFPI antigen in plasma is entirely caused by the enhancement of free TFPI. We then applied the TFPI chromogenic assay to the lipoprotein-depleted fraction to assess the activity of free TFPI. The activity was 0.11+/-0.03 and 0.36+/-0.08 U/ml before and after heparin, respectively (a 3.6-fold increase) while the activity of bound TFPI did not increase at all. We suggest that this method may be an alternative to gel filtration for measuring free TFPI activity, and might be of value in the search for TFPI abnormalities in patients with thrombosis.

Anticoagulants↗
PubMed1998

A cross-over pharmacokinetic study of a double viral inactivated factor IX concentrate (15 nm filtration and SD) compared to a SD factor IX concentrate.

A double blind randomized cross-over multi-center study has been conducted to compare the pharmacokinetic and coagulation activation markers of high-purity factor IX concentrate subjected to both solvent/ detergent (SD) treatment and 15 nm-filtration (FIX-SD-15) with the licensed product subjected only to solvent-detergent (FIX-SD). This filtration process allows the elimination of small particles, such as non-enveloped viruses (i.e., hepatitis A and parvovirus B19). Eleven severe hemophilia B patients (FIX coagulant activity <2 IU/dl) received one infusion of 60 IU/kg of FIX-SD and one infusion of 60 IU/kg of FIX-SD-15 at least at 10 days interval. Blood samples were obtained before and at various time up to 72 h after infusion. The decay curves of factor IX (FIX:C and FIX:Ag) were evaluated by a model independent method. Bioequivalence was found between the two concentrates using the Schuirmann test. The mean FIX:C and FIX:Ag recovery of FIX-SD-15 was 1.08 and 0.89 IU/dl/IU/kg respectively with a mean half-life of 33.3 h for FIX:C and 25.6 h for FIX:Ag. Six months after initial enrollment, pharmacokinetic parameters were similar in the 7 patients tested. There was no significant variation of prothrombin fragment 1+2 and thrombin-antithrombin complexes measured up to 6 h after infusion, indicating that there was no activation process after administration of FIX. In conclusion, these data demonstrate that the introduction of a 15 nm filtration does not alter the pharmacokinetic profile of a well characterized SD FIX concentrate while providing additional viral safety.

Adolescent↗
PubMed1997

Effect of advanced glycation end product-modified albumin on tissue factor expression by monocytes. Role of oxidant stress and protein tyrosine kinase activation.

Diabetes is associated with a hypercoagulable state that contributes to macrovascular complications, including cardiovascular events. The glycation reaction, a consequence of chronic hyperglycemia, has also been implicated in the pathogenesis of diabetic complications. Glycated proteins have receptors on monocytes and generate reactive oxygen species that can regulate the expression of a number of genes. As abnormal monocyte expression of tissue factor (TF), the main initiator of the coagulation cascade, is responsible for thrombosis in a number of clinical settings, we studied the effect of glycated albumin on monocyte TF expression. Mononuclear cells were incubated with glycated albumin for 24 hours, and monocyte TF activity was measured with a plasma recalcification time assay; TF antigen was measured by ELISA and TF mRNA by RT-PCR. Glycated albumin induced blood monocyte expression of the procoagulant protein TF at the mRNA level. Oxidative stress appeared to be involved in this effect, as the antioxidant N-acetylcysteine diminished TF mRNA accumulation in stimulated monocytes. Hydroxyl radicals, which may be generated inside cells from H2O2 via the Fenton reaction, also appeared to be involved in this effect, as hydroxyl radical scavengers downregulated TF activity and antigen levels (but not TF mRNA). Finally, the involvement of activated protein tyrosine kinase in the transmission of the signal from the membrane to the nucleus was suggested by the inhibitory effect of herbimycin A. These results point to a new mechanism for the hypercoagulability often described in diabetic patients and suggest that antioxidants or protein tyrosine kinase inhibitors might be of therapeutic value in this setting.

Acetylcysteine↗
PubMed1996

Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low-molecular-weight heparin.

The incidence of antibodies to heparin-PF4 complexes (H-PF4) has been evaluated in patients who were under heparin therapy for more than 7 days: 109 patients treated with unfractionated heparin (UH) and 100 patients with low-molecular-weight heparin (LMWH). The presence of antibodies was identified in 17% of the former group and 8% of the latter. In both the UH and the LMWH groups, IgM antibodies were found in all but four patients who showed IgA antibodies. IgG isotypes were only detected in five patients and were consistently associated to either IgM or IgA antibodies. The follow-up of H-PF4 antibodies in 76 patients treated with UH from 1 to > or = 12 days showed a relationship between the incidence of antibodies and the duration of therapy. Despite the presence of anti-H-PF4 antibodies there was no thrombocytopenia (<150 10(9)/L) in the patients. A significant drop of platelets requiring the discontinuation of heparin was observed, however, in three patients, but their platelet count consistently remained >150 10(9)/L. Our study demonstrates that the induction of antibodies to H-PF4 is a frequent phenomenon in patients treated with UH or with LMWH. The absence of thrombocytopenia and of clinical complications in these patients demonstrates that other conditions must be associated with H-PF4 antibodies for inducing type II HIT: optimal concentrations of heparin and PF4 in the blood circulation to allow the formation of macromolecular H-PF4 complexes, presence of activated platelets that present an increased binding of H-PF4 complexes, increased expression of FcgammaRIIA receptors, or presence of their H 131 phenotype. We conclude that the measurement of antibodies to H-PF4 complexes allows the detection of heparin-treated patients at risk of developing type II HIT.

Autoimmune Diseases↗
PubMed1996

Activation of coagulation and fibrinolysis in heatstroke.

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 42.3 +/- 0.2 degrees C) pre- and postcooling and compared with 8 heatstressed and 23 normal controls. Comparing heatstroke patients with normal controls, TAT, fibrin monomers, PAP and D-Dimer were elevated to (median (range)) 16.5 (4-1000) versus 3.5 (2-7.2) micrograms/l p < 0.001, 16 (4-113) versus 2 (2-9) nM p < 0.001; 3300 (1000-36500) versus 255 (136-462) micrograms/l p < 0.001 and 0.72 (0.22-64.8) versus 0.15 (0.05-0.25) microgram/ml p < 0.01 respectively. Plasminogen decreased to 81% (34-106); PAP, TAT and D-Dimer correlated significantly with hyperthermia (r = 0.577, p = 0.02; r = 0.635, p = 0.01; r = 0.76, p = 0.003). Postcooling PAP decreased to 545 (260-850) micrograms/l p < 0.005, TAT 10 (6-70) micrograms/l, and fibrin monomers 22 (18-86) nM remained unchanged. Heatstressed controls showed mild but significant increase in all markers. Activation of coagulation and fibrinolysis occurs early and is profound and sustained in heatstroke. Cooling seems to attenuate the activation of fibrinolysis only, however, this requires confirmation in a larger study population.

Aged↗
PubMed1995

Recombinant hirudin (HBW 023): biological data of ten patients with severe venous thrombo-embolism.

This study reports on the biological data of ten patients with acute venous thrombo-embolism. They were treated for 5 days with continuous intravenous infusion of a fixed dose (0.05 mg/kg/hr) of a recombinant hirudin (r-H HBW 023 Behringwerke, Germany). The plasma level of r-H (HBW 023), assessed by an anti-factor IIa amidolytic activity, was stable after Day 2 and showed considerable individual variations. It correlated with APTT ratio, suggesting that this test is a reliable tool to monitor therapy. In contrast, thrombin time was constantly over 120 sec (control 15 sec) and consequently was not a useful parameter. Prothrombin time showed a slight, but significant, prolongation, which was correlated with the increase of APTT ratio. There was no bleeding time prolongation, platelet count, or ATIII level decrease. Levels of thrombin-antithrombin III complexes, and D-dimers, which were high in all patients on admission, decreased during the course of the treatment but remained abnormal on Day 5, showing an ongoing hemostasis and fibrinolysis activation: this is consistent with the delayed, but only slightly decreased thrombin generation evidenced by thrombin generation test performed on Day 3. These results suggest that thrombin inhibition by rH-hirudin at this dosage is only partial, which allows the generation of traces of thrombin needed for the feed-back thrombin production generated by factor V and VIII activation.

Adult↗
PubMed1995

Antibodies to macromolecular platelet factor 4-heparin complexes in heparin-induced thrombocytopenia: a study of 44 cases.

As heparin-PF4 (H-PF4) complexes are the target for antibodies associated to heparin-induced thrombocytopenia (HIT), an ELISA has been developed and optimised for testing antibodies binding to H-PF4. This test was consistently negative in 50 healthy subjects (A492 < 0.3) and 35 patients with other causes of thrombocytopenia (A492 < 0.5). In contrast, 43 out of 44 HIT patients showed antibodies to H-PF4 (A492 = 1.70 +/- 0.81) including 5 patients with a negative platelet aggregation test. In one patient with HIT, antibodies to H-PF4 were already present at day 7, whereas platelet counts dropped < or = 100 x 10(9)/l only at days 11-12. Surprisingly, among 41 patients under heparin for > 7 days, 5 showed antibodies to H-PF4, without HIT. These findings underline the major interest of this ELISA for the early diagnosis of HIT. We also showed that LMWH as well as other sulphated polysaccharides can bind to HIT antibodies in the presence of PF4 and that their reactivity is dependent on the molecular weight and the sulphation grade. The mechanism for HIT involves platelet PF4 receptors which bind the macromolecular H-PF4 complexes formed in the presence of a well defined heparin/PF4 ratio.

Adolescent↗
PubMed1995

Anti-vascular endothelial cell antibodies (AECA): comparison of two assay methods and clinical applications.

Vascular endothelial cells may be a target for autoantibodies (AECAs) against membrane antigens that are constitutively expressed, induced or bound to their surface. To test this hypothesis, we used an enzyme-linked immunosorbent assay (ELISA) with two types of human endothelial cells as the substrate, i.e., human umbilical cord vein endothelial cells (HUVECs) or the hybrid cell line EAhy-926 obtained by fusion of HUVECs with the bronchial carcinoma cell line A549. A comparative functional study of these two cell types demonstrated that EAhy-926 cells produced only small amounts of VIII von Willebrand factor and tissular factor, did not contain Weibel Palade bodies visible under the electron microscope, and expressed ICAM-1 and selectin E in levels of no more than 15% of those expressed by human umbilical cord vein endothelial cells both after stimulation by bacterial lipopolysaccharide and under basal conditions. However, the two assay methods yielded similar IgG AECA titers when used on sera from patients with rheumatoid vasculitis or antiphospholipid syndrome. These antibodies did not exhibit cytotoxicity for cord vein or EAhy-926 cells. They were not specific for endothelium, since their activity decreased by a mean of 40% after incubation of sera with the epithelial cell line A549. A cross-sectional study of 565 sera demonstrated that anti-vascular IgG and IgM AECAs reactive with EAhy-926 cells occurred mainly in patients with dermatomyositis (IgG, 58%; IgM, 22%), systemic scleroderma (IgG, 48%; IgM, 18%), primary Sjögren's syndrome (IgG, 44%; IgM, 12%) and secondary and primary systemic vasculitides (IgG, 38%; IgM, 18%) including Wegener's granulomatosis. A longitudinal study in patients with Wegener's granulomatosis showed that AECAS were predictive of disease activity.

Antibodies↗
PubMed1994

Interleukin-10 and pentoxifylline inhibit C-reactive protein-induced tissue factor gene expression in peripheral human blood monocytes.

Fibrin deposition is an integral feature of the inflammatory response. In response to C-reactive protein (CRP), an acute-phase reactant, blood monocytes synthesize and express tissue factor (TF), the main initiator of blood coagulation. We report the inhibitory effect of interleukin 10 (IL-10) and that of pentoxifylline, a methyl xanthine derivative, on monocyte expression of TF activity, TF protein and TF mRNA in response to CRP. These agents may be of use in diseases where a TF-induced prothrombotic state is detrimental.

C-Reactive Protein↗
PubMed1993

Interleukin-10 inhibits endotoxin-induced tissue factor mRNA production by human monocytes.

In Gram-negative septic shock, human monocytes synthesize and express on their cytoplasmic membrane tissue factor (TF), a potent activator of the coagulation cascades. The role of TF in triggering disseminated intravascular coagulation (DIC) in these patients appears to be clear. We report the suppressive effect of interleukin-10 (IL-10) on endotoxin-induced TF activity and antigen levels, and on the expression of TF mRNA levels in human monocytes. These results emphasize the potential therapeutic value of this cytokine in septic shock, a condition still associated with a high mortality rate.

Humans↗
PubMed1993

Treatment of severe venous thrombo-embolism with intravenous Hirudin (HBW 023): an open pilot study.

Recombinant Hirudin (rH) is an anticoagulant agent with a specific antithrombin activity independent of antithrombin III. We report the results of the first open pilot study on the curative treatment of acute venous thrombo-embolism (VTE) with rH (HBW 023) in ten patients. The dose of rH tested was 0.07 mg/kg (i.v. bolus) followed by 0.05 mg kg-1 h-1 (i.v. infusion) for 5 days, without activated partial thromboplastin time (APTT) adjustment. Within the trial, no death, VTE recurrence or major bleeding was observed; lung scan pulmonary vascular obstruction improved from 44 to 37%, whereas the venographic Marder score was unchanged; APTT ratio ranged between 1.2 and 2.8. The dose of rH assessed in this study seems to be safe and efficient in the treatment of acute VTE.

Aged↗