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Le Touquet – Paris-Plage, France

Mechoulan A.,Nantes University Hospital Center | Kaplan C.,Laboratoire dImmunologie Plaquettaire | Muller J.Y.,Nantes University Hospital Center | Branger B.,Reseau Perinatal Securite Naissance des Pays de la Loire | And 4 more authors.
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2011

Objectives. The aim of this study was to review recent multicenter data on antenatal management of anti-HPA-1a fetal alloimmune thrombocytopenia and, based on this retrospective study and on recent literature, to evaluate if FBS modified the obstetrical management. Material and methods. This retrospective study in France includes 23 pregnancies in 21 women who had a previous thrombocytopenic infant due to anti HPA-1a alloimmunization. All pregnant women received intravenous immunoglobulin (IVIG) treatment, with or without corticosteroids. Fetal blood sampling (FBS) was performed before any therapy (four cases) or during pregnancy (nine cases). Results. Infants whose mother received treatment had a significantly higher neonatal platelet count than the corresponding sibling (p = 0.003). In eight cases, therapy was started late during pregnancy. In three cases, treatment was discontinued 3 or 4 weeks before birth, and this was associated with a poorer result. No in utero intracranial hemorrhage was recorded in the infants for whom maternal therapy continued to term. Adverse effects were not observed in any case. All babies were delivered by cesarean even when FBS was performed. One emergency cesarean was performed for fetal bradycardia after FBS. Conclusion. This study confirmed that maternal therapy with intravenous immunoglobulin for fetal alloimmune thrombocytopenia gives satisfactory results. It also showed that a less invasive approach, especially a reduction in the number of fetal blood samples, is possible without deleterious consequences. This observation suggests also to start IVIG early during pregnancy and to continue treatment up to delivery. © 2011 Informa UK, Ltd.

Moncharmont P.,Laboratoire dImmunologie Plaquettaire | Rigal D.,Laboratoire dImmunologie Plaquettaire
Transfusion Clinique et Biologique | Year: 2014

Purpose of the study. - Use of matched red blood cell (RBC) concentrates is imperative in patients with RBC allo-antibodies (Abs) and whenplatelet (PLT) specific allo-Abs are present additional difficulties occur for PLT transfusions. In order to evaluate the prevalence of the PLT andRBC allo-Abs association, a study on patients with PLT specific allo-Acs was performed. This association is not a rare event.Patients and methods. - In the database of a PLT immunohaematology laboratory, patients with PLT specific allo-Abs were selected and thepresence and specificity of RBC allo-Abs was evaluated.Results. - Six hundred and eighty seven patients (673 females, 14 males) with PLT specific allo-Abs were found. Six hundred and seventy-fivepatients (98.3%) had PLT specific allo-Abs with only one specificity. Anti-HPA-5b was the most frequent (539 cases). Twenty-nine (4.2%) patientshad also RBC allo-Abs, including 27 females (93.1%) and two males. Seventy (58.6%) had RBC allo-Abs with only one specificity, 10 several andtwo unknown. Among the first, RBC allo-Abs directed against Rhesus blood group antigens were predominant (11 cases [64.7%]). Among the29 patients with associated PLT and RBC allo-Abs, 15 (51.7%) were 50 or more years old and 14 (48.3%) under 50.Conclusion. - In PLT specific alloimmunized patients, detection of RBC alloimmunization is not a rare event. When RBC and PLT transfusionsare required, the supply of matched RBC and PLT concentrates is more difficult. © 2014 Published by Elsevier Masson SAS.

Jallu V.,Laboratoire dImmunologie Plaquettaire | Dusseaux M.,Laboratoire dImmunologie Plaquettaire | Panzer S.,Medical University of Vienna | Torchet M.-F.,Center des Hemophiles | And 4 more authors.
Human Mutation | Year: 2010

Glanzmann thrombasthenia (GT) is an autosomal recessive inherited bleeding disorder characterized by an impaired platelet aggregation due to defects in integrin αIIbβ3 (ITGA2B, ITGB3), a fibrinogen receptor. Mutations from 24 GT patients and two carriers of various origins, Caucasian, North-African and Asian were characterized. Promoter and exon sequences of αIIb and β3 genes were amplified and directly sequenced. Among 29 identified mutations, 17 new allelic variants resulting from nonsense, missense and deletion/insertion mutations were described. RNA alterations were evaluated by using Web servers. The αIIb p.S926L, p.V903F, and β3 p.C38Y, p.M118R, p.G221D substitutions prevented complex expression at the surface of COS-7 cells by altering the αIIb or the β3 subunit structure. As shown by free energy analyses applied on the resolved structure of αIIbβ3 and structural modeling of the mutant, the p.K253M substitution of β3 helped to define a key role of the K253 in the interaction of the αIIb β-propeller and the β3 β-I domains. finally, the αIIb p.Q595H substitution allowed cell surface expression of the complex but its corresponding c.2800G > T mutation is predicted to alter normal RNA splicing. In conclusion, our study yielded the discovery of 17 new GT allelic variants, revealed the key role of K253 of αIIb for the αIIbβ3 complex formation and provides an additional example of an apparently missense mutation causing a splicing defect. © 2009 Wiley-Liss, Inc.

Jallu V.,Laboratoire dImmunologie Plaquettaire | Poulain P.,French Institute of Health and Medical Research | Poulain P.,University Paris Diderot | Poulain P.,Sanguine | And 10 more authors.
PLoS ONE | Year: 2012

Background: The HPA-1 alloimmune system carried by the platelet integrin αIIbβ3 is the primary cause of alloimmune thrombocytopenia in Caucasians and the HPA-1b allele might be a risk factor for thrombosis. HPA-1a and -1b alleles are defined by a leucine and a proline, respectively, at position 33 in the β3 subunit. Although the structure of αIIbβ3 is available, little is known about structural effects of the L33P substitution and its consequences on immune response and integrin functions. Methodology/Principal Findings: A complete 3D model of the L33-β3 extracellular domain was built and a P33 model was obtained by in silico mutagenesis. We then performed molecular dynamics simulations. Analyses focused on the PSI, I-EGF-1, and I-EGF-2 domains and confirmed higher exposure of residue 33 in the L33 β3 form. These analyses also showed major structural flexibility of all three domains in both forms, but increased flexibility in the P33 β3 form. The L33P substitution does not alter the local structure (residues 33 to 35) of the PSI domain, but modifies the structural equilibrium of the three domains. Conclusions: These results provide a better understanding of HPA-1 epitopes complexity and alloimmunization prevalence of HPA-1a. P33 gain of structure flexibility in the β3 knee may explain the increased adhesion capacity of HPA-1b platelets and the associated thrombotic risk. Our study provides important new insights into the relationship between HPA-1 variants and β3 structure that suggest possible effects on the alloimmune response and platelet function. © 2012 Jallu et al.

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