Biotin-Labeled RBC Survival in Thalassemia and Impact of Treatment.
Notice bibliographique
Résumé
Abstract Determination of red blood cell (RBC) survival in the peripheral blood, to evaluate the efficacy of pharmacological agents that augment fetal hemoglobin (HbF) and total hemoglobin (Hb) in patients with beta-thalassemia, has not been implemented. We report the use of biotin labeling, a nonisotopic, safe and effective method to determine the erythrocyte lifespan, proven to be equivalent to 51Cr. We studied RBC survival in 9 Hemoglobin E-β-thalassemia (ET) patients, 4 thalassemia intermedia (TI) patients and compared RBC survival to normal control. Repeat measures were performed in 3 ET patients while on hydroxyurea (HU) treatment at 15–19 mg/Kg/day. RBC from 30 ml blood were ex-vivo biotinylated under sterile conditions using EZ-Link Sulfo-NHS-Biotin (Pierce), and re-infused to the patient as described before (Franco et al,1998). At set time points, the number of biotinylated cells was determined in small blood samples by flowcytometry using fluorescently labeled strepavidin. All patients tolerated the procedure well without an indication of re-infusion induced infection or anti-biotin antibody related hemolysis. The presence of biotinylated cells in the circulation was followed until only 0.05-0.08% biotinylated cells could be detected. The data were mathematically fitted to 100–100*[1-(1/T)*t]exp(-kt), where t is the time point, T is the extinction time, and k the exponential rate of RBC removal. The control data showed a linear removal rate (k=0), and a T of 100 days (R=0.95), consistent with a normal red cell life span. In the 9 ET and 4 TI patients, a faster disappearance of biotinylated cells was noted, and the number of surviving (biotinylated) cells in the population followed an exponential pattern, consistent with random removal (k=0.033, R= 0.97). Mean survival was 43±11 and 36±15 days, respectively. The 3 patients who received 10–12 months of HU treatment had a mean 0.8 gr/dL increase in their Hb and 20% increase in HbF. However, no difference was found in the RBC survival curves of these patients (k=0.034, R= 0.97), as compared to the non treated patients. One patient who was treated with HU and Erythropoietin (500u/Kg x3/wk) and had a 1.6 gr/dL increase in hemoglobin and RBC survival analysis showed the biotinylated cells to follow a similar survival curve. While these results cannot exclude a longer survival in selected cells, specifically those containing higher HbF, the overall effect of HU treatment has not proven to prolong the lifespan of labeled thalassemia erythrocytes. These results indicate that biotin label provides RBC survival characteristics in thalassemia patients. The method has advantages over 51Cr, including lack of radioactivity, avoiding labeling elution, low expense and recovery of labeled cells after prolonged time in the circulation. Moreover, the method is a valuable tool to measure effect of various treatments on the survival characteristics of the thalassemia erythrocytes. Preliminary findings indicate that despite the effect of HU on an increase in HbF and a mild to moderate increase in total Hb, the overall thalassemic erythrocyte lifespan has not increased, suggesting other mechanisms for these results including erythroid expansion, improved effective erythropoiesis and cell selection.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».