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T Lecompte

Publications and source records attributed to T Lecompte.

At least 37 records · Page 2Linked to original sources
PubMed2002

Low molecular weight heparin-loaded polymeric nanoparticles: formulation, characterization, and release characteristics.

The aim of the present work was to investigate the preparation of low molecular weight heparin (LMWH) nanoparticles (NP) as potential oral heparin carriers. The NP were formulated using an ultrasound probe by water-in-oil-in-water (w/o/w) emulsification and solvent evaporation with two biodegradable polymers [poly-epsilon-caprolactone, PCL and poly(D,L-lactic-co-glycolic acid) 50/50, PLGA] and two non-biodegradable positively charged polymers (Eudragit RS and RL) used alone or in combination. The mean diameter of LMWH-loaded NP ranged from 240 to 490 nm and was dependent on the reduced viscosity of the polymeric organic solution. The surface potential of LMWH NP prepared with Eudragit polymers used alone or blended with PCL and PLGA was changed dramatically from strong positive values obtained with unloaded NP to negative values. The highest encapsulation efficiencies were observed when Eudragit polymers took part in the composition of the polymeric matrix, compared with PCL and PLGA NP exhibiting low LMWH entrapment. The in vitro LMWH release in phosphate buffer from all formulations ranged from 10 to 25% and was more important (two- to threefold) when esterase was added into the dissolution medium. The in vitro biological activity of released LMWH, determined by the anti-factor Xa activity with a chromogenic substrate, was preserved after the encapsulation process, making these NP good candidates for oral administration.

Acrylic Resins↗
PubMed2002

[Arterial thrombogenesis: the crucial role of platelets].

Better understanding of platelet function helps not only the integration of many available data, because the fact that platelets play a decisive role in arterial thrombosis, but also to determine the pharmacological management of these phenomena. Globally, platelets aggregate at the site of atherosclerotic plaque rupture allowing the generation of thrombin in the haemodynamic conditions which exist in this region.

Arteries↗
PubMed2002

[Treatment with lepirudin in heparin-induced thrombocytopenia. A case report].

We report the case of a 71 old woman presenting a bilateral massive pulmonary embolism with intraventricular right thrombus complicating heparin induced thrombocytopenia (HIT) persistent after one month of conventional anticoagulant processing. We underline the effectiveness of lepirudin (Refludan) in the curative processing of pulmonary embolism allowing here to avoid a complex surgical thromboembolectomy. We evoke the place of this molecule in the curative therapeutic strategy of HIT with thrombotic phenomena.

Aged↗
PubMed2001

[Neonatal renal vein thrombosis in a heterozygous carrier of both factor V Leiden and prothrombin mutations].

UNLABELLED: We report a case of renal vein thrombosis, treated with heparin and thrombolytic therapy, in a patient who was heterozygous for both factor V Leiden and prothrombin mutations. CASE REPORT: A full-term infant was treated with heparin and fibrinolytics at the fourth day of life because of renal vein thrombosis, inferior vena cava thrombosis and adrenal hemorrhage. After four days of treatment, the repermeabilization was complete but a renal atrophy developed. The investigation for congenital coagulation disorders revealed a heterozygous mutation for both factor V Leiden and prothrombin. CONCLUSION: Search for inborn blood coagulation disorders should be systematic in the newborn infant with venous thrombosis because of the risk of recurrence, even in the presence of a known acquired risk factor. The thrombolytic treatment improves the prognosis.

Adrenal Gland Diseases↗
PubMed2001

Effects of three Hb-based oxygen-carrying solutions on neutrophil activation in vitro: quantitative measurement of the expression of adherence receptors.

BACKGROUND: Hb-based oxygen carriers (HbOCs) are currently under investigation as RBC substitutes. These solutions have vasoactive properties and may modify the behavior of the RBC in vitro. The effects of these agents on other blood cells have not been extensively investigated. The aim of this study was to evaluate the potential effect(s) of three differently modified HbOCs on the activation of PMNs. STUDY DESIGN AND METHODS: Whole blood from humans was incubated with Hb dextran-benzene-tetracarboxylate, alphaalpha-Hb, or o-raffinose-poly-Hb for 15, 30, and 60 minutes. The expression of adherence receptors CD62L, CD18, and CD11b, which reflects the activation state of the neutrophils, was assessed in vitro by a direct immunofluorescence method using calibration beads measured by flow cytometry. RESULTS: The observed expression of each of the three adherence receptors for each solution at each time point was similar to that noted with the RPMI control. Decreases in CD62L and increases in CD18 expression were noted at 15 minutes of incubation but, when those values were compared to the values obtained with TNFalpha as the positive control of PMN activation, the profile of expression of adherence receptors obtained with HbOC solutions did not conform to the expected activation profile of PMNs. CONCLUSION: Hb solutions modified by a variety of methods, as obtained and employed in this study, did not appear to activate neutrophils in vitro.

Aspirin↗
PubMed2001

The role of platelet factor 4 in platelet aggregation induced by the antibodies implicated in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a severe side effect of heparin treatment. Recent studies using immunological methods demonstrated that antibodies contained in plasma, or in purified total immunoglobulin (Ig)G from patients suffering HIT, recognize as target antigen the complex heparin/platelet factor (PF4). In the present study, the role of PF4 in in-vitro platelet aggregation induced by purified total IgG or platelet-poor plasma from patients suffering HIT was investigated. In order to demonstrate the functional role of PF4, an anti-PF4 antibody that specifically blocked PF4 was used. In an experimental system composed of washed platelet suspension, incubation of F(ab')2 fragments (0.125 microg/ml) of the polyclonal anti-PF4 antibody resulted in complete inhibition of platelet aggregation triggered by purified total IgG from patients suffering HIT and heparin. In platelet-rich plasma, a significantly higher concentration (4.25 microg/ml) of the anti-PF4 F(ab')2 was required to inhibit platelet aggregation induced by HIT-PPP and heparin. Intermediate concentrations of the anti-PF4 antibody partially inhibited platelet aggregation. In plasma milieu, the concentration of PF4 was about five-fold higher in comparison with that measured in the purified system. The intensity of platelet aggregation depended on the concentration of HIT-IgG. Platelet aggregation was abolished in the presence of high concentrations of heparin (superior or equal to 10 IU/ml). The present study shows that PF4 is essential for platelet aggregation triggered by the antibodies related to HIT in the presence of heparin. The concentration of PF4 that is available to bind with heparin or with the HIT-related antibodies is critical for platelet aggregation induced by HIT antibodies.

Antibodies↗
PubMed2001

Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontané; FFAACS).

BACKGROUND: A combination of low-dose aspirin with anticoagulants may provide better protection against thromboembolic events compared to anticoagulants alone in high-risk patients with atrial fibrillation. OBJECTIVE: Evaluation of the preventive efficacy against nonfatal thromboembolic events and vascular deaths of the combination of the oral anticoagulant fluindione and aspirin (100 mg) in patients with high-risk atrial fibrillation. METHODS: A multicenter, placebo-controlled, double-blind, randomized trial was conducted at 49 investigating centers in France. Atrial fibrillation patients with a previous thromboembolic event or older than 65 years and with either a history of hypertension, a recent episode of heart failure or decreased left ventricular function were included in the study. Patients were treated with fluindione plus placebo (i.e. anticoagulant alone) or fluindione plus aspirin (i.e. combination therapy), with an international normalized ratio target of between 2 and 2.6. The combined primary endpoint was stroke (ischemic or hemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. The secondary endpoint was the incidence of hemorrhagic complications. RESULTS: The 157 participants (average age 74 years; 52% women; 42% with paroxysmal atrial fibrillation) were followed for an average of 0.84 years. Three nonfatal thromboembolic events were observed (1 in the anticoagulation group, 2 in the combination group) and 6 patients died (3 in the anticoagulation group, 3 in the combination group), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe hemorrhagic complications (1 in the anticoagulation group, 2 in the combination group). Nonfatal hemorrhagic complications occurred more often in the combination group (n = 10, 13.1%) compared to the anticoagulation group (n = 1, 1.2%) (p = 0.003). CONCLUSION: The combination of aspirin with anticoagulant is associated with increased bleeding in elderly atrial fibrillation patients. The effect on thromboembolism and the overall balance of benefit to risk could not be accurately assessed in this study due to the limited number of ischemic events.

Administration, Oral↗
PubMed2001

[Cutaneous delayed hypersensitivity reactions to heparins and heparinoids].

INTRODUCTION: Due to cross-reactions between unfractionated heparins, low-molecular-weight heparins and sometimes heparinoids, cutaneous delayed hypersensitivity reactions might be a problem for the choice of therapeutic alternative. We report on two cases of sensitization to heparins and heparinoids. OBSERVATIONS: One woman developed localized skin reaction to a low-molecular-weight heparin, then a generalized maculopapular rash when an intravenous injection of unfractionated heparins was performed. The second patient had a localized then extended reaction to a low-molecular-weight heparin and was referred for the choice of a well tolerated method to obtain anticoagulation during a pulmonary surgery. METHODS: Patch tests, prick tests, intradermal and subcutaneous tests were performed with several unfractionated heparins, low-molecular-weight heparins, danaparoid and lepirudin in both cases. RESULTS: In the first case, tests performed with both heparins and heparinoid were positive and the use of lepirudin was proposed if anticoagulation was necessary. In the second case the subcutaneous danaparoid injection induced a localized reaction on the injection site. Danaparoid injections were continued associated with localized applications of dermocorticoids without any side effect. DISCUSSION: Cutaneous delayed hypersensitivity reactions occur on the injection site but can also be generalised. Cross reactions might be unexpected therefore skin-tests are necessary to guide the choice of a therapeutic alternative. In case of intolerance to both heparins and heparinoids various solutions may be proposed such as the application of topical corticosteroids on the injection site or the administration of hirudins. There is no cross sensitization between heparins and hirudins, but the use of hirudins is restricted and requires specific monitoring.

Drug Eruptions↗
PubMed2001

Beta2-glycoprotein I binding to platelet microparticle membrane specifically reduces immunoreactivity of glycoproteins IIb/IIIa.

We have investigated beta2-glycoprotein I (beta2GPI) binding to platelet-derived microparticles (PMP) and its effect on GPIIb/IIIa. PMP were isolated from washed human platelets after stimulation with A23187, and analyzed by surface plasmon resonance spectroscopy. Beta2GPI as well as activated protein C (APC) or annexin V bound to PMP-coated sensorchips, demonstrating exposure of anionic phospholipids on immobilized PMP. Beta2GPI binding was impaired by calcium and occurred in a concentration-dependent manner with apparent k(on) = 2.6 x 10(4) M(-1) s(-1) and k(off) = 4.4 x 10(-3) s(-1), corresponding to a KD value of 1.7 x 10(-7) M. When analyzed by flow cytometry, the binding of certain mAbs specific for GPIIb and/or GPIIIa was reduced in the presence of beta2GPI but not of APC or annexin V, whereas the binding of anti-GPIb or anti-P-selectin mAbs, or of soluble fibrinogen remained unchanged. These results suggest a broad but specific influence of beta2GPI on GPIIb/IIIa immunoreactivity, and indicate that beta2GPI may act as a modulator of GPIIb/IIIa-dependent functions of PMP.

Antibodies, Monoclonal↗
PubMed2001

A naturally occurring point mutation in the beta3 integrin MIDAS-like domain affects differently alphavbeta3 and alphaIIIbbeta3 receptor function.

We have investigated the effect of a new Leu196Pro mutation, identified in the MIDAS-like domain of the beta3 integrin subunit in a patient with type II Glanzmann thrombasthenia, on beta3 integrin receptor function. Expression of the mutant beta3Pro196 subunit in CHO cells, either associated with recombinant human alphaIIb or alphav, resulted in normal biosynthesis of beta3 and heterodimerization with alphav or alphaIIb, but selectively interfered with alphaIIbbeta3 maturation and transport to the cell surface. Functional analysis of the beta3 mutant receptors revealed strong inhibition of alphavbeta3-mediated cell spreading on immobilized fibrinogen, focal contact formation, p125FAK phosphorylation and fibrin clot retraction, as opposed to normal alphaIIbbeta3-mediated cell interaction with immobilized fibrinogen, focal contact translocation and signaling. In contrast, antibody- or DTT-activated mutant aIIbbeta3 was unable to bind soluble fibrinogen or the ligand mimetic PAC-1 monoclonal antibody, but underwent a conformational change following RGD peptide binding as demonstrated by AP5-LIBS epitope expression. These results suggest that (1) the highly conserved TL196T motif in the beta3 integrin subunit is located in a domain structurally important for the exposure of a functional binding site for soluble fibrinogen; and (2) that the MIDAS-like contact site in beta3 is not involved in alphaIIbbeta3-mediated cell adhesion to immobilized fibrinogen, while it is essential for alphavbeta3-mediated interaction with this ligand.

Amino Acid Sequence↗
PubMed2001

[New antithrombotic drugs (excluding plasminogen activators].

New platelet antagonists act on the activation by ADP (clopidogrel, ATP analogue) or on the mechanism of aggregation itself, by binding to the IIb/IIIa glycoprotein complex. The new anticoagulants are as follows: saccharide structures such as danaparoïd and the pentasaccharide of antithrombin binding, and direct thrombin inhibitors, such as recombinating hirudines (desirudine, lepirudine), bivalirudine, melagatran.... Other molecular targets are possible, both at platelet and blood clotting levels but, for the moment, the dilemma remains and reinforcement of antithrombotic activity goes hand in hand with a greater decrease in the defensive mechanisms against bleeding. In general, there is no antidote and the products are often associated, which increases the risk of haemorrhage. The research and development in this field are handicapped by the lack of biological tools for pertinent, homogenous, reproducible evaluation of the effects on haemostasis. The present tendency is to do without biological monitoring for adapting dosage in favour of optimisation of the impact in a given situation, perhaps, above all, with respect to the preceding problem.

Anticoagulants↗
PubMed2000

Recombinant hirudin anticoagulation for aortic valve replacement in heparin-induced thrombocytopenia.

PURPOSE: To report the case of a patient with HIT that received a prolonged infusion of r-hirudin (lepirudin; Refludan; Hoechst, France) before, during and after cardiopulmonary bypass (CPB) for aortic surgery. Although administration of r-hirudin for CPB anticoagulation has previously been reported, many questions persist concerning the best therapeutic regimen for CPB anticoagulation as well as the time of onset and the doses for postoperative anticoagulation. CLINICAL FEATURES: A 65-yr-old man was admitted for surgery of aortic stenosis after an episode of acute pulmonary edema complicated by deep venous thrombosis in the context of documented HIT. The patient received r-hirudin for 13 dy before surgery at doses (0.4 mg x kg(-1) bolus followed by 0.15 mg x kg(-1) x hr(-1) continuous infusion) that maintained activated partial thromboplastin time (aPTT) ratios between 2 and 2.5. Anticoagulation for CPB was performed with r-hirudin given as 0.1 mg x kg(-1) i.v. bolus and 0.2 mg kg(-1) in the CPB priming volume. Anticoagulation during CPB was monitored with the whole blood activated coagulation time and ecarin clotting time (ECT) performed in the operating room with values corresponding to r-hirudin concentrations >5 microg x ml(-1) during CPB. Anticoagulation during CPB was uneventful. Two bleeding episodes, related to the r-hirudin regimen and necessitating allogeneic blood transfusion, occurred after surgery. CONCLUSION: This case report confirms previous experience of the use of r-hirudin for anticoagulation during CPB and provides additional information in the context of prolonged r-hirudin infusion before and after CPB.

Aged↗
PubMed2000

Monovalent binding of autoantibodies to beta2-glycoprotein I, detected using surface plasmon resonance at low antigen density.

The precise mechanism of interaction between autoantibodies and beta2-glycoprotein I (beta2GPI) and the experimental conditions to be used for their detection are still under debate. Until now, these interactions have been studied under static conditions. We have investigated the interactions of purified IgG from 25 lupus anticoagulant-positive patients with immobilized beta2GPI under flow conditions by real-time analysis based on surface plasmon resonance technology. Sensor chips were coated with purified human beta2GPI coupled to dextran via amino groups at low densities (1.4, 1.8 or 2. 4 ng beta2GPI/mm2). Four patients' IgG displayed efficient binding and had the highest so-called antiphospholipid IgG levels by enzyme-linked immunosorbent assay (ELISA) and the highest absorbance values in an anti- beta2GPI ELISA at a beta2GPI density reported to be around 12 ng/mm2. Binding of antibodies to the beta2GPI sensor chips proved to be dependent upon the IgG concentration and beta2GPI density and was inhibited by a rabbit antibody against beta2GPI. Similar association and dissociation profiles were observed for the four efficient binders. The fast rate of dissociation limited the binding of autoantibodies to beta2GPI and was highly suggestive of a monovalent association, confirmed by binding of Fab fragments under similar experimental conditions. In conclusion, monovalent binding of low-affinity antibodies to beta2GPI immobilized at a density as low as 1.8 ng/mm2 could be detected using surface plasmon resonance.

Animals↗