Summary
A multicenter study was set up to evaluate the prevalence, clinical and biological significance of antiphosphatidylethanolamine antibodies (aPE) in thrombotic patients with or without the ...main known clinical and biological risk factors for thrombosis. APE and antibodies, defined as the laboratory criteria of antiphospholipid syndrome (APS) -lupus anticoagulant, anticardiolipin and anti-beta2-GPI antibodies were measured in 270 patients with thrombosis (234 venous and 37 arterial) and 236 matched controls. APE were found in 15% of thrombotic patients compared to 3% of controls (p<0.001) with no predominant isotype, no association with the main known clinical or biological risk factors for thrombosis neither with a type of thrombosis, arterial or venous. In a multivariate logistic regression analysis of antibodies, aPE showed the highest association with thrombosis (odds ratio OR: 4.2, p<0.001). Moreover, using a multivariate analysis in a case-control subgroup study on 158 patients, IgGaPE were found to be significantly associated with venous thrombosis (OR:6;p=0.005). Interestingly, 25 of the 40 aPE-positive patients (63%) were negative for the APS laboratory criteria. Most of them (21/25) had venous thrombosis, recurrent in ten of them. Four patients also suffered from early or late miscarriages. Our results underline the strength of the association between the presence of aPE and thrombosis and suggest their measurement in thrombotic patients, especially when lupus anticoagulant, anticardiolipin or anti-beta2-GPI antibodies are absent.
Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide ...heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.
Coupled transfers of aroma compounds and water vapour were investigated by varying the relative humidity gradient of storage (50% or 90%) of two paper packaging at 25 degrees C. These papers differed ...in their coating surface: both were identically impregnated then supercalendered, and only one was twice coated on both sides with a synthetic barrier substance. Permeability and solubility coefficients were determined. The coating treatment was more effective to decrease the permeabilities of water vapour and ethyl ester than the effect of RH. On the contrary, the RH modified the water content of the treated papers and affected more strongly their permeability and solubility to cis-3-hexenol and benzaldehyde. The cis-3-hexenol transfer through the non-coated paper and the benzaldehyde transfer through the coated paper decreased due to a probable competition with sorbed water although it increases for the cis-3-hexenol of a plasticisation phenomenon.
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.
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.
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.
The precise mechanism of interaction between autoantibodies and β
2
‐glycoprotein I (β
2
GPI) 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 β
2
GPI under flow conditions by real‐time analysis based on surface plasmon resonance technology. Sensor chips were coated with purified human β
2
GPI coupled to dextran via amino groups at low densities (1·4, 1·8 or 2·4 ng β
2
GPI/mm
2
). 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‐ β
2
GPI ELISA at a β
2
GPI density reported to be around 12 ng/mm
2
. Binding of antibodies to the β
2
GPI sensor chips proved to be dependent upon the IgG concentration and β
2
GPI density and was inhibited by a rabbit antibody against β
2
GPI. Similar association and dissociation profiles were observed for the four efficient binders. The fast rate of dissociation limited the binding of autoantibodies to β
2
GPI 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 β
2
GPI immobilized at a density as low as 1·8 ng/mm
2
could be detected using surface plasmon resonance.
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