Role of P-Selectin and GPIbα in the Fast and Delayed Clearance of Transfused Platelets.
Notice bibliographique
Résumé
Abstract Platelets become activated during preparation and storage of platelet concentrates (PCs) for transfusion. Flow cytometric assays of platelet activation can be employed for quantifying in vitro quality of PCs. It remains, however, unclear whether the level of in vitro platelet activation in stored PCs correlates with in vivo survival of the platelets after transfusion. Platelet surface glycoprotein (GP) Ibα and P-selectin (CD62) can be involved in regulation of posttransfusion PC clearance, mediating adhesive interactions of platelets with counter-receptors on leukocytes and endothelial cells. Recently, we described a rabbit model for analyzing posttransfusion kinetics of human PCs (Leytin et al, Transfusion42:711, 2002, Transfusion43:983, 2003). In the present work, we used this validated model for studying the implication of CD62 and GPIbα expression in posttransfusion PC clearance. Platelet activation in vitro was determined by flow cytometry using anti-CD62 and anti-GPIbα antibodies. PC clearance in vivo was evaluated in rabbits with inhibited reticuloendothelial system, as measured by 0.5 hr (R0.5), 24 hr (R24) and total (R∑) platelet recoveries, and survival time (ST). Correlations were analysed between in vitro assays of platelet activation and in vivo clearance of conventional (Day 2–5) and outdated (Day 7–8) PCs stored at 22°C, and refrigerated PCs. We found that the binding of anti-CD62 antibody was significantly increased in outdated and refrigerated PCs compared to conventional PCs, reflecting an increased exposure of CD62 on the platelet surface. In contrast, binding of anti-GPIbα antibody was significantly decreased during prolonged and refrigerated PC storage. The clearance of conventional (Day 2–5) PCs from the circulation can be described by a biphasic survival curve. The first (early) phase of platelet clearance is characterized by fast (≥ 14 x 109 platelets per hour) platelet removal, whereas the second (delayed) phase has a much slower rate of platelet clearance (approximately 0.4 x 109 platelets per hour). The biphasic survival curves were also obtained for outdated and refrigerated PCs, and were employed for determining fast (R0.5), delayed (ST and R24) and overall (fast + delayed; R∑) platelet clearance in vivo. We found that when stored PCs are cold-damaged, their in vivo viability decreased significantly, in comparison to conventional PCs, as reflected by the fast, delayed and overall platelet clearances. Viability of Day 7–8 PCs is also decreased, compared to Day 2–5 PCs, but only the fast and overall platelet clearance increased significantly. Negative correlation was observed between in vitro anti-CD62-binding to platelets and their fast, but not delayed, clearance. In contrast, anti-GPIbα-binding showed positive correlations with delayed, but not fast, platelet clearance. Overall clearance correlated better with anti-GPIbα- than with anti-CD62-binding. We also demonstrated that CD62 is shed from the platelet surface after transfusion, whereas GPIbα remains unchanged on the surface of circulating platelets. The data suggest that CD62 exposure during PC storage triggers fast CD62-mediated PC clearance. However, after CD62 shedding during platelet circulation, in vitro GPIbα alterations, such as cleavage, clustering or conformation changes, may determine long-term GPIbα-mediated PC clearance.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| 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 | 0,001 | 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) | 0,001 | 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 source (Gemma direct ou Codex distillé), 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 ».