Platelet Membrane Procoagulation in Preeclampsia
Notice bibliographique
Résumé
Background: Preeclampsia is a hypertensive disorder in pregnancy that results in significant adverse maternal and neonatal outcomes. Platelet activation is involved in the pathophysiology of preeclampsia and contributes to the prothrombotic state of the disorder. The mechanisms which initiate and sustain platelet activation in preeclampsia, and how platelets are involved in the pathogenesis of coagulation abnormalities in preeclampsia remains unclear.Aim: To utilise a systematic analysis of Procoagulant Membrane Dynamics (PMD) to assess platelet procoagulation in normotensive pregnancies and preeclampsia, compared to age-matched non-pregnant female controls. Methods: Platelets were assessed using 4D live-cell imaging, immunoassay, flow cytometry and impedance aggregometry. Study participants were healthy, non-diabetic, normotensive, non-pregnant controls, (NP, N=9), normotensive pregnant controls (PC, N=9), and pregnant women with preeclampsia (PEE, N=8). Result: Platelets of preeclamptic patients were significantly activated under basal conditions and showed major remodelling of the open canalicular or dense tubular system. Compared to NP and PC controls, PEE platelets showed a marked decrease in dense granule release, and total exposed phosphatidylserine (PS)-laden surface as well as a decreased whole-blood aggregation in response to high concentration collagen stimulation. Notably, in patients who were pregnant, we visualized in both plasma and peripheral whole blood, freely suspended platelet microthrombi ranging from 10-15 µm radius but were more in PEE participants (~75%) than in the normal pregnant controls (~22%). These microthrombi showed fibrin deposits in between procoagulant platelets with ballooned membranes. Unstimulated PEE platelets showed more than a 2-fold increase in the membrane expression of the facultative glucose transporter GLUT3 which normally reside within the intracellular membrane of alpha granules. Multiplex immunoassay for inflammatory markers confirmed the elevation of previously unreported i-309 and C-TACK inflammatory cytokines in PEE participants. Discussion: We elucidated a platelet-based mechanism of procoagulation in patients with preeclampsia; and demonstrated that platelets were highly activated in the basal, resting state in preeclampsia. Platelet hyperactivation in preeclampsia is complex; there is evidence of procoagulant morphologic membrane changes and p-selectin expression, yet platelets were less able to adhere to exposed collagen to form primary hemostatic plugs. Additionally, novel platelet activation and inflammatory markers such as GLUT3, i-309, and C-TACK cytokines requires further study to understand how they mediate the platelet activation process and the pathophysiology of preeclampsia. Conclusion: Platelet hyperactivation and increased GLUT3 membrane expression may contribute to the progression of preeclampsia, and to the thrombotic and coagulopathic maternal complications of the disease. The platelet activation process itself may provide biomarkers for staging and phenotyping preeclampsia and for the prediction of its severity, clinical manifestations, and disease progression. Disclosures Lee: Takeda: Consultancy, Honoraria, Speakers Bureau; Bayer: Honoraria. Poon:Takeda: Other: honoraria for advisory board meeting attendance; Pfizer: Other: honoraria for advisory board meeting attendance; Novo Nordisk: Other: honoraria for advisory board meeting attendance; Roche: Other: honoraria for advisory board meeting attendance; Bayer: Other: honoraria for advisory board meeting attendance, Research Funding; Bioverative/Sanofi: Other: honoraria for advisory board meeting attendance; CSL-Behring: Other: honoraria for advisory board meeting attendance, Research Funding.
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 | 0,001 | 0,001 |
| 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 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 ».