Procoagulant Platelet Subpopulation Formation in Whole Blood: Correlation with Whole Blood Clotting Time and 5-Year Mean Bleeding Score in Individuals with Factor VIII Deficiency.
Notice bibliographique
Résumé
Abstract Abstract 4022 Poster Board III-958 Different clinical phenotypes are often observed among individuals with hemorrhagic or thrombotic disorders despite the presence of the same mutation and/or factor levels suggesting that additional genetic and/or environmental factors influence clinical presentation. As thrombin plays a central role in hemostasis, factors that affect an individual's ability to generate thrombin may lead to an increased risk of hemorrhage or thrombosis. The goal of this study was to assess procoagulant platelet formation in individuals with hemophilia A using a rapid, whole blood flow cytometric assay of prothrombinase complex assembly on platelets described previously. In this assay, Ca2+-dependent factor Xa binding to activated platelets is used as a marker of thrombin generating potential as it has been shown previously to correlate with platelet prothrombinase activity in a washed platelet system. Procoagulant platelet subpopulation formation in 15 men with varying degrees of factor VIII-deficiency was evaluated and compared to two independent measures of hemostatic competence: a 5-year mean bleeding score and whole blood clot time. In these individuals, the % activated platelets binding factor Xa in whole blood varied from 2.35 – 9.0% (n = 30), which is consistent with what is observed in unaffected individuals (1.5 – 41.5%, n = 136). Bleeding was scored independently by two experienced hemophilia nurses and one hematologist at Centre Hospitalier Universitaire Sainte Justine based on each individual's bleeding history, including hemarthroses, soft tissue hematoma, and annual factor VIII usage, and averaged. The 5-year mean bleeding scores in these individuals ranged from 0 – 20.4. Linear regression analyses indicated that in this population the % activated platelets binding factor Xa correlated indirectly with the 5-year mean bleeding score, where individuals with lower bleeding scores (i.e. less bleeding episodes and/or factor VIII usage) generated larger procoagulant platelet subpopulations. The time to clot formation in a tissue factor-dependent, contact pathway-suppressed whole blood clotting assay described previously, was also determined. The clot time, which was determined visually, and ranged from ∼3 – 7 min, also correlated indirectly, though less well, with the % activated platelets binding factor Xa in whole blood (r = -0.23). Thus, consistent with what was observed with the bleeding score, those individuals who clotted more quickly (i.e. exhibited a greater degree of hemostatic competence) generated more proacoagulant platelets. Platelet procoagulant subpopulation formation was also compared to other hematological measures. An inverse correlation was observed between the % activated platelets binding factor Xa and mean platelet volume (r = -0.347), suggesting that in this population, individuals with smaller platelets (i.e. platelets with fewer prothrombinase binding sites) may generate a greater number of platelets capable of assembling prothrombinase. In contrast, no correlation was observed between whole blood platelet number and % activated platelets binding factor Xa. Interestingly, factor Xa binding was also negatively correlated with plasma levels of factor IX (r = -0.56) and factor V (r = -0.62). Platelet subpopulation formation was also weakly and negatively associated with the aPTT (r = - 0.28). In this small population of individuals with hemophilia A, whole blood platelet factor Xa binding correlates with bleeding phenotype. These observations support the notion that this measurement can be used to predict an individuals propensity to bleed or clot. Disclosures: No relevant conflicts of interest to declare.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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 ».