Platelet Activation Rather Than Apoptosis Contributes Most to the Platelet Storage Lesion during Conventional and Extended Storage of Platelet Concentrates
Notice bibliographique
Résumé
Abstract Platelet storage lesion is a serious problem limiting clinical use of platelet concentrates (PC) after extended and long-term storage. Platelet activation is a well-known manifestation of platelet storage lesion. However, over the last decade, platelet apoptosis has been also recognized in stored PCs and in platelets following exposure to thrombin, calcium ionophores, anti-platelet antibodies and very high shear stresses. The aim of this study was to elucidate the contribution of platelet activation and apoptosis to the platelet storage lesion during conventional (Days 2–5), extended (Days 6–8) and long-term (Days 11–16) PC storage. We prepared seven prestorage-leukoreduced PC by the platelet-rich plasma (PRP) method, stored PC for 2–16 days at 22°C, and used flow cytometry for determining platelet activation as P-selectin (CD62) exposure and platelet apoptosis as depolarization of mitochondrial inner membrane potential (ΔΨm), activation of executioner caspase-3, exposure of phosphatidylserine (PS) and release of apoptotic platelet fragments microparticles (MP). Platelet activation and apoptotic responses were also determined in fresh (Day 0) PRP using thrombin titration. We found a significant increase of platelet activation under conventional PC storage for 2–5 days (38.6 ± 3.1% CD62 positive cells, P < 0.0001). With extended (Days 6–8) storage, platelet activation was increased to 66.5 ± 5.3% and reached the maximal level of 92.0 ± 1.1% after 11–12 storage days (P < 0.0001). In contrast, ΔΨm depolarization and caspase-3 activation did not increase in comparison with Day 0 platelets, even after PC storage for 12 days (P > 0.05) and storage for 13–16 days was required for significant triggering these apoptotic events (P < 0.05-0.0001). Similarly, although we observed a slight increase of PS exposure (5–10%) and MP release (9–11%) during PC storage for 2–12 days, incubation for 13–16 days was required for a stronger (30–60%) stimulation of these apoptotic manifestations (P < 0.001-0.0001). Paired comparison between the effects of PC storage on CD62 exposure and apoptotic events clearly demonstrated for all storage times a significantly higher level of platelet activation than levels of ΔΨm depolarization, caspase-3 activation, PS exposure and MP release (P < 0.01-0.0001). Furthermore, we found that when fresh (Day 0) PRP was treated with different thrombin doses, ranging from 0.05 to 10 U/ml, a much higher maximal level of platelet activation (~90%) was reached, in comparison to the level of apoptosis (30–40%), and 100- to 200-fold lower dose of thrombin were required for maximal induction of activation (0.05–0.1 U/ml) than for stimulation of apoptosis (10 U/ml). Taken together, these data indicate that (i) during PC storage, platelet activation is triggered much earlier than platelet apoptosis, (ii) platelet activation rather than apoptosis contributes most to the platelet storage lesion during conventional (Days 2–5) and extended (Days 6–8) PC storage whereas during long-term (Days 13–16) storage both responses are involved in platelet deterioration, and (iii) platelet activation and apoptosis are different phenomena; they may be induced by different mechanisms and/or require quite different levels of triggering stimuli.
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 | 0,000 | 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) | 0,001 | 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 ».