Intravenous (IV) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term ...results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight IVIgG reinfu-sions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 × 109/L (range 72 to 836 × 109/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two IVIgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last IVIgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 × 109/L; range: 150 to 250 × 109/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 × 109/L). Five of the 7 responders at D90 kept a platelet count above 50 × 109/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an IVIgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated IVIgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bone allografts are commonly used by orthopedists to provide a mechanical support and template for cellular colonization and tissue repair. There is an increasing demand for bone graft substitutes ...that are safe and easy to store but which are equally effective in supporting new bone growth. In this study, we compared three different human bone allografts: (1) the cryopreserved allograft (frozen), (2) the gamma-irradiated and cryopreserved allograft (γ-irradiated), and (3) the solvent dehydrated and γ-irradiated-processed bone allograft (Tutoplast(®) Process Bone TPB). Human mesenchymal stromal cells (hMSCs) have the potential to differentiate into osteogenic, chondrogenic, and adipogenic lineages. Our results showed that hMSC seeding efficiency was equivalent among the three bone allografts. However, differences were observed in terms of cell metabolism (viability), osteoblastic gene expression, and in vivo bone formation. Frozen allografts had the higher frequency of new bone formation in vivo (89%). Compared with frozen allografts, we demonstrated that TPB allografts allowed optimal hMSC viability, osteoblastic differentiation, and bone formation to occur in vivo (72%). Further, the frequency of successful bone formation was higher than that obtained with the γ-irradiated allograft (55%). Moreover, after hMSC osteoinduction, 100% of the TPB and frozen allografts formed bone in vivo whereas only 61% of the γ-irradiated allografts did. As healthcare teams around the world require bone-grafting scaffolds that are safe and easy to store, the TPB allograft appears to be a good compromise between efficient bone formation in vivo and convenient storage at room temperature.
Les modèles murins d’allo-immunisation anti-globule rouge (GR) montrent qu’une stimulation de la voie TLR3, 4heures précédant la transfusion, peut favoriser l’allo-immunisation. Les études vaccinales ...in vitro montrent que les réponses immunitaires sont réduites si l’administration de l’antigène précède ou suit de 6heures l’injection d’agoniste de TLR. Nous posons l’hypothèse que le délai entre l’injection de l’agoniste TLR et la transfusion influence l’intensité de l’allo-immunisation.
Pour étudier cette hypothèse, nous avons utilisé le modèle murin B10BR. Ces souris ont reçu une injection de Poly(I:C) à différents temps avant d’être transfusées avec des GR de souris HOD (expression de HEL sur les GR). Après transfusion, la présence d’anticorps anti-HEL a été testée dans le sérum. Le phénotype des cellules dendritiques (DC) présentant HEL et des LT CD4+ spléniques spécifiques de HEL a été évalué.
Cette étude révèle que le taux d’anticorps anti-HEL est maximal à 7jours de délai. Nous montrons que plusieurs caractéristiques des DC et LT CD4+ sont associées à la production accrue d’anticorps lorsque l’injection est éloignée de la transfusion : (1) une modification du ratio des DC CD8α+/CD8α− présentant HEL au profit des CD8α+ ; (2) une synthèse accrue d’IL12 par ces DCs CD8α+ ; (3) et une forte expression de CD134, CD40 ou CD44 sur les LT CD4+ spécifiques de HEL.
Chez l’homme, le rôle des infections virales n’est pas connu dans l’allo-immunisation anti-GR. De plus, dans les maladies liées aux GR comme la drépanocytose, l’environnent inflammatoire et l’activation des TLR pourraient être centraux dans l’allo-immunisation et pris en compte pour la prévention de l’allo-immunisation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We have previously demonstrated that immune platelet destruction observed in an AIDS‐free HIV‐infected patient was associated with the presence of a cross‐reactive antibody recognizing both ...HIV‐glycoprotein (gp)120 and platelet gpIIIa (CD61). We have now investigated the presence of such antibodies in other HIV‐infected patients, together with the molecular structure of the cross‐reactive epitope. Platelet gpIIb/IIIa antibodies were characterized in sera from HIV‐infected patients with immune thrombocytopenic purpura by means of an ELISA and a radioimmunoprecipitation procedure (RIP). The platelet antibodies were purified and tested for their ability to recognize HIV‐gp. We also tried to characterize the antibody target epitope on HIV‐gp120 using recombinant gp and synthetic peptides. IgG with anti‐gpIIb/IIIa activity were detected, by means of an ELISA with purified gpIIb/IIIa, in 101/138 (73%) sera from HIV‐infected patients with immune thrombocytopenic purpura. The platelet antibodies were purified from 23 sera by absorption/elution on purified immobilized platelet gpIIb/IIIa, and recognition of gpIIIa was confirmed in eight cases with a RIP. Furthermore, the presence of a cross‐reactive antibody between HIV‐gp120 and platelet gpIIIa was demonstrated in 18/18 patients (including the eight with a confirmed gpIIIa antibody) by the ability of the serum HIV‐gp160/120 antibodies to bind to purified gpIIb/IIIa. The cross‐reactive epitope was shown to be independent of the carbohydrate moieties of gp120, since deglycosylation of two recombinant (r)‐gp120s did not abolish antibody binding. However, the antibody did not recognize synthetic gp120 peptides spanning 355 of the 516 amino acids of gp120, particularly the four regions exhibiting sequences of four or five consecutive amino acids that are identical between r‐gp120 and gpIIIa. Our results thus support the hypothesis that the cross‐reactive antibody recognizes the conformational structure of gp120. These results strongly suggest that molecular mimicry between HIV‐gp120 and platelet gpIIIa may be important in the pathogenesis of immune thrombocytopenia in AIDS‐free HIV‐infected patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The need to adapt red blood cells concentrates management in surgery blocs and resuscitation to the changes of the legal framework has lead to a collective approach to improve practices. Gathered by ...the regional hemovigilance coordinators of the Drass Ile-de-France (regional office of health and social actions), representatives of doctors' ordering transfusions and hemovigilance correspondents of the Assistance publique-Hôpitaux de Paris and representatives of the EFS (French blood establishment) Ile-de-France, together with representatives of the Afssaps (French health products safety agency), have coordinated an assessment of local transfusion practices in surgery blocs and resuscitation that have to be compliant. Each hospital then offered local improvement actions, approved by regional and national instances. We present this original and collective approach of assessing practices leading to offers that both respond to a legal framework and improve blood products flows without damaging transfusion security.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Treatment of adults with autoimmune thrombocytopenic purpura (AITP) is based more on individual experience than on results of controlled studies. We compared intravenous immunoglobulin with high-dose ...methylprednisolone in untreated adults with severe AITP and assessed efficacy of subsequent oral steroids compared with placebo. Primary outcome was number of days with platelet count greater than 50×109/L within the first 21 days.
We did a randomised multicentre trial based on a 2×2 design. 122 adults with severe AITP (platelet count ⩽ 20×109/L) were randomly assigned to receive either intravenous immunoglobulin or high-dose methyl-prednisolone on days 1–3 (randomisation A), and then to receive either oral prednisone or placebo (randomisation B) on days 4–21. Analysis was by intention to treat.
Six patients were excluded from the analysis. The number of days on which platelet counts were above 50×109/L was 18 in 56 patients receiving intravenous immunoglobulin and 14 in 60 receiving high-dose methylprednisolone (p=0·02). Percentage of patients who had platelet counts over 50×109/L on days 2 and 5 was 7% and 79%, respectively, in the intravenous immunoglobulin group compared with 2% and 60%, respectively, in the high-dose methylprednisolone group (p=0·04). During the second treatment period, prednisone was more effective than placebo for all short-term endpoints. Patients who received intravenous immunoglobulin and prednisone had platelet count greater than 50×109/L for 18·5 days (p=0·005), and those treated with high-dose methylprednisolone and prednisone had this count for 17·5 days.
Intravenous immunoglobulin and oral prednisone seems to be more effective than high-dose methylprednisolone and oral prednisone in adults with severe AITP, although the latter treatment is effective and well tolerated.
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DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SIK, UILJ, UKNU, UL, UM, UPCLJ, UPUK, VSZLJ
La prévention des hémolyses post-transfusionnelles chez les drépanocytaires est conditionnée par notre capacité à prévenir l’allo-immunisation et les conflits antigène–anticorps. Cette étude montre ...l’importance de mettre en place une organisation transfusionnelle adaptée au profil immunohématologique particulier des drépanocytaires pour leur garantir une sécurité transfusionnelle optimale.
Les données immunohématologiques de 206 adultes drépanocytaires transfusés en dehors de l’urgence ont été analysées, ainsi que le phénotype des concentrés globulaires (CGR) délivrés. Cinquante-quatre pour cent des patients ont un phénotype D+C−E−c+e+. Pour prévenir l’allo-immunisation anti-C et anti-E, 26 % de CGR D−C−E−c+e+ ont été transfusés à ces patients D+. Quarante-sept pour cent des patients ont un historique d’allo-immunisation, alors que seulement 15 % ont une recherche d’agglutinines irrégulières positive le jour de l’inclusion, les anticorps non décelables étant souvent dangereux. Enfin, cette étude montre la fréquence importante d’anti-D chez les sujets D+ et d’anti-C chez les sujets C+, posant la question du caractère partiel des antigènes D et C.
Pour une sécurité transfusionnelle optimale des patients drépanocytaires et une meilleure adéquation entre phénotypes des receveurs et phénotypes des CGR disponibles, trois points dans l’organisation transfusionnelle doivent être améliorés : la promotion du don au sein des populations afro-antillaises doit être renforcée pour disposer de CGR D+C−E−c+e+ et éviter d’utiliser la ressource limitée de CGR D−C−E−c+e+ ; les données immunohématologiques des patients doivent être accessibles aux prescripteurs et transfuseurs, afin d’éviter les accidents immuno-hémolytiques par restimulation ; enfin, la recherche par biologie moléculaire des antigènes variants d’intérêt transfusionnel doit être mise en place chez les donneurs et receveurs afro-antillais.
Prevention of hemolytic transfusion reactions depends upon our capacity to prevent allo-immunization and conflicts between antigens of transfused red blood cells and antibodies produced by the recipient. In this study, we show that to secure transfusion of sickle cell disease patients, it is necessary to take into account their immunohematologic characteristics in the organization of transfusion.
Immunohematological data of 206 chronically transfused patients have been collected as well as phenotypes of transfused units. In order to prevent allo-immunization against C and E antigens for patients typed D+C−E−c+e+ (56%), 26% of the transfused units were D−C−E−c+e+. We found that 47% of the patients had a history of allo-immunization, whereas only 15% produced an antibody the day of inclusion in the study. The non-detectable antibodies were frequently known as dangerous for transfusion. Finally, this study shows the frequency of anti-D in D+ patients and anti-C in C+ patients, pointing out the question of partial antigens.
To insure optimal transfusion safety for sickle cell disease patients, three points have to be improved: blood donation within the Afro-Caribbean community living in France, access to history of immuno-hematological data, detection of variant antigens, especially within the RH blood system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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